OBJECTIVE: To compare the effect of octreotide (a long-acting somatostatin analog) to that of antidiarrheal therapy plus placebo on large-volume refractory AIDS-associated diarrhea. DESIGN: A randomized controlled trial. SETTING: Referral-based clinic and hospital in a tertiary care center. PATIENTS: Twenty male patients with AIDS and refractory diarrhea, with stool volume > 1000 ml/day who failed to improve after initial supportive management. All patients finished the study. INTERVENTIONS: Patients were randomly given either octreotide in doses of 100, 200 and 300 micrograms subcutaneously every 8 h, or high doses of loperamide and diphenoxylate orally plus placebo subcutaneously for 10 days. MAIN OUTCOME MEASURES: Bowel movements and stool volume were registered before and every day after treatment by the patients themselves and the nursing personnel. RESULTS: Patients from both groups were similar for age, time of AIDS diagnosis, duration of diarrhea and etiology. Baseline mean bowel movements per day (9.4 +/- 2.8 in the octreotide group versus 10 +/- 3.1 in controls) and baseline mean stool volume (2753 +/- 840 versus 2630 +/- 630 ml/day, respectively) were similar in both groups before therapy (P < 0.05). Mean bowel movements per day after 10 days of therapy was 2.1 +/- 1.6 in the octreotide group versus 7 +/- 3 in controls (P < 0.05). Mean stool volume after 10 days of therapy was 485 +/- 480 in the octreotide group versus 1080 +/- 420 ml/day in controls (P < 0.05). Complete response (stool volume < 250 ml/day) was observed in two patients from the octreotide group and none from controls; partial response (decrease > 50% in stool volume) in four and two; and no response (decrease < 50% or no change) in four and eight (P < 0.05), respectively. Side-effects occurred in eight out of 10 octreotide patients and three out of 10 controls (P < 0.05), but none were significant to result in discontinuation of medication. CONCLUSION: Octreotide proved to be superior to conventional therapy in this short-term treatment of large-volume refractory AIDS-associated diarrhea.